Inefficient toll-like receptor-4 stimulation enables Bordetella parapertussis to avoid host immunity

Daniel N. Wolfe, Anne M. Buboltz, Eric Thomas Harvill

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The recognition of bacterial lipopolysaccharide (LPS) by host Toll-like receptor (TLR)4 is a crucial step in developing protective immunity against several gram negative bacterial pathogens. Bordetella bronchiseptica and B. pertussis stimulate robust TLR4 responses that are required to control the infection, but a close relative, B. parapertussis, poorly stimulates this receptor, and TLR4 deficiency does not affect its course of infection. This led us to hypothesize that inefficient TLR4 stimulation enables B. parapertussis to evade host immunity. In a mouse model of infection, B. parapertussis grew rapidly in the lungs, but no measurable increase in TLR4-mediated cytokine, chemokine, or leukocyte responses were observed over the first few days of infection. Delivery of a TLR4 stimulant in the inoculum resulted in a robust inflammatory response and a 10- to 100-fold reduction of B. parapertussis numbers. As we have previously shown, B. parapertussis grows efficiently during the first week of infection even in animals passively immunized with antibodies. We show that this evasion of antibody-mediated clearance is dependent on the lack of TLR4 stimulation by B. parapertussis as co-inoculation with a TLR4 agonist resulted in 10,000-fold lower B. parapertussis numbers on day 3 in antibody-treated wild type, but not TLR4-deficient, mice. Together, these results indicate that inefficient TLR4 stimulation by B. parapertussis enables it to avoid host immunity and grow to high numbers in the respiratory tract of naïve and immunized hosts.

Original languageEnglish (US)
Article numbere4280
JournalPloS one
Volume4
Issue number1
DOIs
StatePublished - Jan 26 2009

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Bordetella parapertussis
Toll-Like Receptor 4
Immunity
immunity
Antibodies
Pathogens
Chemokines
Lipopolysaccharides
Animals
Infection
infection
Cytokines
antibodies
Bordetella bronchiseptica
Bordetella pertussis
Toll-like receptor 4
Whooping Cough
chemokines
Infection Control
respiratory system

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Wolfe, Daniel N. ; Buboltz, Anne M. ; Harvill, Eric Thomas. / Inefficient toll-like receptor-4 stimulation enables Bordetella parapertussis to avoid host immunity. In: PloS one. 2009 ; Vol. 4, No. 1.
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Inefficient toll-like receptor-4 stimulation enables Bordetella parapertussis to avoid host immunity. / Wolfe, Daniel N.; Buboltz, Anne M.; Harvill, Eric Thomas.

In: PloS one, Vol. 4, No. 1, e4280, 26.01.2009.

Research output: Contribution to journalArticle

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